Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.796479
Title: The distribution of interferon-alpha in normal human tissues
Author: Khan, Nizam-ud-Din
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1990
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Abstract:
The presence of interferon-alpha (IFN-alpha) in human tissues has been described extensively in viral infections. In the last decade many workers have also shown the presence of low levels of IFN-alpha in conditions other than viral infections. While the precise origin of the synthesis of low levels of IFN-alpha in these physiological conditions has not been clearly defined, some evidence has suggested that macrophages may be involved. In an attempt to find the likely source of IFN-alpha in physiological conditions, an initial study was carried out in which the cellular distribution of immunoreactive IFN-alpha was studied in formalin fixed paraffin embedded normal adult human tissues from 38 different organs using various immunocytochemical techniques. These samples were drawn from over 300 individuals none of whom had evidence of viral infection. Tissue histiocytes from all organs in the body, with the exception of cerebral and cerebellar cortex in brain and renal cortex and medulla, stained positively for IFN-alpha. Kupffer cells, pulmonary alveolar macrophages and lymph node macrophages were also positive for IFN-alpha. Parenchymal cells in some other organs also contained immunoreactive IFN-alpha. These included syncytiotrophoblast in first, second and third trimester placentas, cuboidal lining cells of the choroid plexus in the brain, thyroid follicullar cells, pituitary endocrine cells, adrenocortical cells and parathyroid endocrine cells. These findings are compatible with previous suggestions that IFN-alpha may be synthesized and released in the absence of viral infection and may have a role in normal physiology. The presence of IFN-alpha in most cells of the mononuclear phagocyte system suggests that these cells play a major role in the defence against viral infection. This speculation, however does not preclude other possible roles for IFN-alpha, such as modulation of cell growth, major histocompitability antigen expression etc. The demonstration of immunoreactive IFN-alpha in formalin fixed paraffin embedded normal adult human tissues prompted other studies. In the first of these studies the cellular distribution of immunoreactive IFN-alpha was studied in formalin fixed paraffin embedded normal human autopsy tissues from 32 fetuses (7-42 weeks gestation) and 20 infants (aged from a few hours to 24 months). This study was performed to test the hypothesis that microbes have a role in switching on IFN-alpha synthesis. Fetal tissues are "germ free" while the infants had been exposed to a normal microbial flora. Immunoreactive IFN-alpha was first seen at 9 weeks gestation in macrophages in the fetal liver and thereafter was seen in macrophages in most other organs except in kidneys and cerebral and cerebellar cortex. When infant lungs were compared with fetal lungs a statistically significant increase in the number of macrophages (P< 0.0001, Mann-Whitney test) and the percentage of these cells expressing IFN-alpha (P <0.0005, Mann-Whitney test) was noted in infant lungs. No such changes were observed in spleen, liver and thymus following birth. These findings suggested that there is a basal level of IFN-alpha production by macrophages, which is not dependent on microbial products, but that such microbial products can enhance synthesis of this cytokine. Immunoreactive IFN-alpha was also demonstrated in parenchymal cells of thyroid gland, choroid plexus in brain, anterior pituitary gland and adrenal gland in the fetal and infant tissues. These findings were almost identical to those seen in adult tissues. In a separate study an attempt was made to extract, detect and quantify IFN-alpha in human tissues using protein extraction and an immunoradiometric assay kit for the detection of IFN-alpha. 20 placentas (14-42 weeks gestation) obtained fresh within 1-2 hours of vaginal delivery, 4 specimens of amniotic fluid obtained at the time of caesarean section from 37-39 weeks gestation pregnancies, 10 samples of choroid plexus and cerebral cortex, 11 thyroid glands and 9 fetal adrenal glands from adult and fetal autopsies performed within 10-24 hours of death were studied. IFN-alpha was detected in 9 placentas, 1 adult thyroid gland and all 4 amniotic fluids. However, this study failed to detect IFN-alpha in the remaining placentas and adult thyroid glands and in all choroid plexuses, cerebral cortex and fetal adrenal glands. Formalin fixed paraffin embedded tissues from these organs did show immunoreactive IFN-alpha in cells using the immunocytochemical techniques. Finally an attempt was made to detect IFN-alpha messenger RNA (mRNA) in normal human tissues using an in situ hybridization method.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.796479  DOI: Not available
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